Covid-19 Vaccine Associated Myocarditis and Pericarditis in Norway

This is a national multicenter study in Norway investigating of individuals with Covid-19 vaccine associated myocarditis (VAM) and pericarditis in Norway.

The main objective is to validate the reported possible cases of Covid-19 vaccine associated myo-and pericarditis in Norway as well as investigate for predisposing factors and risk factors for developing these vaccine adverse events.

Furthermore, patients with confirmed Covid-19 VAM, will be invited to participate in a prospective cohort study, investigating for cardiac long-term adverse effects 1 year and 2 years after vaccine-associated myocarditis.

Study Overview

• Status: Enrolling by invitation
• Conditions: Myocarditis
• Intervention / Treatment: Other: no intervention

Detailed Description

Myocarditis and pericarditis following vaccination with Covid-19 vaccines has been reported as rare but unexpected and potentially severe vaccine adverse events.

In Norway, all vaccines administrated are registered in the national vaccine registry (SYSVAK). All in-hospital diagnoses are reported in a national diagnosis registry (NPR). These complete national high-quality registers allow linking diagnosis of myocarditis and pericarditis to vaccine data (date, product, dose number) on an individual level.

Oslo University Hospital, in collaboration with the Norwegian Institute of Public Health and the Norwegian Medicines Agency, will perform a study consisting of 2 parts:

Part 1 "Validation study":

Eligible patients for inclusion are all individuals with suspected / reported Covid - 19 vaccine associated pericarditis and myocarditis in Norway from 2021 and onwards. Patients will be identified by linking data from the Norwegian Patient registry NPR (ICD-10 diagnostic codes for pericarditis and myocarditis) and the Immunization registry (SYSVAK) (< 90 days since vaccination). The diagnosis of Covid-19 vaccine associated pericarditis and myocarditis will then be confirmed or rejected by medical record search according to international accepted Brighton criteria. The Brighton collaboration criteria provide evidence levels of diagnostic certainty of myocarditis and pericarditis based on cardiac signs and symptoms, cardiac enzymes, ECG findings, imaging studies and histopathology.The criteria is used to distinguish between suspected, probable and confirmed diagnosis of myocarditis and pericarditis. Patients with another more likely reason for confirmed myocarditis or pericarditis by Brighton will not be classified with Covid-19 vaccine associated myocarditis (VAM) or pericarditis, respectively.

Part 2 "Clinical follow-up study" All patients identified in the validation study with confirmed Covid-19 VAM will be invited to participate in the prospective clinical follow-up study (all age groups, both sexes, all geographical areas of Norway). Inclusion wil be by informed consent. Data collection, symptom reporting and cardiac examinations (clinical examination, ECG, 24 hours Holter ECG, echocardiography, cardiac magnetic resonance imaging) will be performed at 1 and 2 years after a diagnosis of Covid -19 VAM. Blood analyses will be performed and a blood sample stored in a biobank in consenting participants. Clinical endpoints will be collected at 1 and 2 years follow-up.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Covid-19 vaccine associated myocarditis and pericarditis

Description

Part 1 Individuals identified with possible Covid-19 vaccine associated myocarditis and pericarditis, by linkage of diagnosis of myocarditis and pericarditis (from Norwegian Patient Registry, NPR) and vaccination data (Immunization registry, SYSVAK).

Part 2.

Inclusion Criteria:

• Confirmed myocarditis (definite, probable, possible) by Brighton criteria < 90 days after either Covid-19 vaccine.

Exclusion Criteria:

• Other more likely cause of myocarditis, including Covid-19 infection.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Covid-19 vaccine associated myocarditis; No intervention	Other: no intervention; No intervention. Observational study only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of myocardial scar	Quantification of myocardial scar by cardiac magnetic resonance (CMR).	1 year post myocarditis
Reduced myocardial function	Assessment of myocardial function by echocardiography and CMR	1 year post myocarditis
Presence of supraventricular arrhythmias	Presence, frequency and type supraventricular arrhythmias detected on ECG and 24 hours Holter ECG recording	1 year post myocarditis
Presence of ventricular arrhythmias	Presence, frequency and type of ventricular arrhythmias detected on ECG and 24 hours Holter ECG	1 year post myocarditis
Persisting cardiac symptoms.	Participant reporting shortness of breath,chest pain, dizziness, syncope, fatigue.	2 years post myocarditis
All cause death	Register death by cause	1 year post myocarditis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persisting cardiac symptoms.	Participant reporting shortness of breath,chest pain, dizziness, syncope, fatigue.	2 years post myocarditis
Presence of myocardial scar	Quantification of myocardial scar by cardiac magnetic resonance (CMR).	2 years post myocarditis
Reduced myocardial function	Assessment of myocardial function by echocardiography and CMR	2 years post myocarditis
Presence of supraventricular arrhythmias	Presence, frequency and type supraventricular arrhythmias detected on ECG and 24	2 years post myocarditis
Presence of ventricular arrhythmias	Presence, frequency and type of ventricular arrhythmias detected on ECG and 24 hours	2 years post myocarditis
All cause death	Register death by cause	2 years post myocarditis

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Norwegian Institute of Public Health; Norwegian Medicines Agency
• Investigators: Principal Investigator: Nina E Hasselberg, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Vaccine side effect; Long term cardiac follow up
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Myocarditis; Pericarditis
• Other Study ID Numbers: 434476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No